1. Field of the Technology
The invention relates to the field of multimodal medical devices and methods for the diagnosis and treatment of cancer, cardiac and cardiovascular disease.
2. Description of the Prior Art
In traditional cardiology and oncology, disease diagnosis and treatment procedures are usually separate. Separate diagnosis and treatment increases the cost and cannot provide timely treatment, which may increase morbidity in some cases. A system which can diagnose and treat diseases simultaneously will greatly decrease the cost and provide timely treatment, which may prevent death from the disease.
Thermal therapy with its relative low cost, few side-effects and short procedure time has been widely used in clinical studies, as an alternative treatment for various diseases besides surgery. Termal therapy here refers to both thermal therapy where tissue is heated to higher temperature and cryotherapy where tissue is cooled to lower temperature. However, without an imaging guidance and a monitoring technique, the accuracy and success rate of a procedure is limited. Consider the problems experienced in the following fields.
1. Cardiology
Coronary artery disease (CAD)/peripheral artery disease (PAD) is the result of the accumulation of plaque within the walls of the coronary arteries that supply oxygen and nutrients to the myocardium. Plaque is made up of fat, cholesterol, calcium, fibrous tissue, and other substances, and over time, the plaque can harden and narrow or block the lumen of the artery. The major cause (86%) of cardiovascular death in heart attacks and the major cause (45%) of deaths from brain aneurysms are from less obtrusive plaques known as “vulnerable plaques” that rupture suddenly and trigger a blood clot or thrombus that blocks blood flow.
For the treatment of CAD/PAD, open surgical revascularization is the standard method of peripheral revascularization because of its high long-term potency rates. However, surgical bypass procedures are associated with periprocedural morbid events, such as wound infection. Endovascular therapy is an alternative to conventional surgical revascularization. However, current endovascular approaches, such as percutaneous transluminal angioplasty (PTA) and stenting, have suboptimal long-term potency. Conventional PTA is limited by high rates of vascular recoil, dissection, and restenosis, especially in the cases of infrainguinal intervention. Although stenting improved periprocedural success by successfully treating vascular recoil and dissection, it still produces unacceptably high restenosis rates and low long-term potency rates, especially for below-the-knee lesions.
Thermal balloon angioplasty (thermoplasty) is a new therapeutic approach for PAD/CAD. It involves the use of cold or heat therapy with angioplasty to treat atherosclerotic plaque, which might improve outcomes and decrease the need for re-intervention. During cryoplasty, the surgeon inserts a balloon catheter into an artery with plaque. Once the balloon catheter reaches the plaque site, the freezing agent is inflated into the balloon. The inflation of the agent due to the higher temperature opens the occluded vessel while freezing the contacted plaques at certain low temperatures. The super-cooling kills local proliferated smooth muscle cells and other unwanted cells while maintaining the vessel structure.
During the heating treatment of the atherosclerosis, high temperature ablates the plaque. Use of the high temperature can easily open up the occluded region in the blood vessel and spare the need of stents. Thermoplasty has been proved to have much better patency rate and lower rate of restenosis.
Besides, according to recent findings, smooth muscle cell abnormal proliferation is involved in both atherosclerosis and restenosis, and these proliferated cells are more sensitive to both low temperature and hyperthermia than the endothelial cells. Thus, through accurately controlled thermal dosage delivery, the endothelium of the blood vessels may also be kept intact during the treatment, which could not been achieved by current treatment modalities and may ensure a much lower restenosis rate after the treatment. Furthermore, the peak temperature rise in vessel wall could be localized in smooth muscle layer while sparing the vascular endothelium through combined RF heating and cooling flow inside a balloon.
Accurate detection of plaque lesions is the first and necessary step in preventing the lethal consequences of atherosclerosis. Traditional angiography only shows an image of the lumen of the vessels; it is impossible for the angiographic image to tell exactly where the atherosclerotic plaque is located. A reliable method for the identification of individuals with atherosclerotic plaques that have a high risk of rupture is fundamental to the selection of patients for vascular intervention. Diagnosis of the latent vulnerability of a plaque lesion relies on tissue structural, chemical compositions, and tissue mechanical properties. The thickness of the fibrous cap, the thickness of the full plaques, the intra-lesion lipid density, tissue mechanical properties are all parameters that correlate with the vulnerability of a lesion.
For over 20 years, intravascular ultrasound (IVUS) imaging has been a standard diagnostic tool for atherosclerosis. IVUS is a catheter-based technique that provides high-resolution, cross-sectional images of the coronary vessel in vivo. In daily clinical practice, IVUS is increasingly used for the visualization of coronary lumen, vessel wall, and atherosclerotic plaque formation. IVUS imaging is performed through cannulation by a catheter with a miniature transducer that emits high-frequency ultrasound, usually in the range of 20 to 50 MHz. As the transducer is moved through the artery, ultrasonic reflections are electronically converted to cross-sectional images. Recent work in IVUS backscatter analysis demonstrated the feasibility and limitation of IVUS to characterize specific lesions and identify plaques that lead to various clinical syndromes. The use of a motorized pull-back device with a defined pull-back speed (0.5 to 1 mm/s) is the established method to image the entire vessel. This permits a volumetric assessment of the vessel and plaque dimensions after longitudinal or 3-dimensional, computer-assisted reconstruction. However, current IVUS has limited resolution and sensitivity to assess the thickness of thin fibrous caps and for plaque classifications.
Recently, optical coherence tomography (OCT) with high resolution, has been applied to intravascular imaging because it enables direct imaging of the thin fibrous cap, circumferential extent of the necrotic cores, and possibly the presence of macrophages in the fibrous cap. All of these are key features of vulnerable atherosclerotic plaque. OCT is a high resolution imaging modality that takes advantage of the short coherence length of broad-band light sources to perform micrometer-scale (μm), cross-sectional imaging of biological tissues. In OCT, imaging contrast originates from sample inhomogeneous scattering properties that are linearly dependent on the sample's refractive indices. OCT offers an axial resolution of 1-15 μm and a penetration depth of around 2-3 mm.
2. Oncology
Thermal therapy has been used for cancer for nearly 50 years. It uses either higher temperature or lower temperature to kill the cancer cells. Compared to other therapies, thermal therapy enables a shorter hospital stay, shorter recovery period, less complications and less pain than with surgery. The induced immunological response by the thermal intrusion offers its great possibility in tumor treatment. However, this high cure rate is not possible in other cancer modalities yet. One reason is the limited high resolution imaging methods for guiding treatment and monitoring treatment at internal body sites to ensure sufficient killing by the thermal treatment, the heating or freezing.
Furthermore, treating tumors with little alteration to the surrounding normal tissue has long been the goal of medical research. In the past two decades, technological advances have brought forth minimally invasive approaches for eliminating undesired tissues. Both cryosurgery and RF heating have attracted a great deal of attention with the help of increased understanding of disease response to freezing/heating and advances in cooling/heating technology. In addition, the use of intra-operative ultrasound guides the placement of cryosurgery probes or the RF/microwave antena. X-ray CT and MRI can also image frozen tissue. However, ultrasound/CT/MRI is limited by its resolution from which it is very difficult to define the fine boundary of the tumor and provide a clear monitoring of tissue deformation under temperature change. OCT gives a ˜5 um resolution visualization of tissue, and OCT catheters broaden its applications, such as in bronchial cancer, prostatic cancer, colon cancer and so on.
Lung Cancer:
Radiotherapy and chemotherapy are the standard treatments for lung cancer but have limited effectiveness in reopening obstructed airways. Patients with obstructed airways are not considered suitable for surgery, the other standard treatment for lung cancer, either. Cryosurgery is one of several techniques that can be used to reopen an obstructed tracheobronchial lumen. Cryosurgery is superior than other techniques because of its low cost, few or no side effects and shorter procedure time (˜20 mins). High temperature ablation has also been used for lung cancer treatment, the elevated temperature induces both apoptosis and necrosis of the tumor cells and spares the normal tissues by accurate control of the thermal energy.
Pancreatic Cancer:
As estimated by the American Cancer Society, about 45,220 Americans will experience pancreatic cancer in 2013, and 38,180 will die from it. Very few patients survive over five years. Conventional surgery usually kills tumor tissue in pancreas but also crucial blood vessel cells are also destroyed. The pancreas is filled with blood vessels. It is very challenging to kill tumor tissue without heavy bleeding or cuting important nerves by conventional surgery. However, there is one encouraging therapy: cryosurgery. Cryosurgery can kill the tumor cells without damaging the blood vessels. The high temperature ablation has also been proved to be a feasible, safe and promising modality for patients with locally advanced and unresectable pancreatic cancer.
Prostate Cancer:
In North America, prostate cancer is the most common noncutaneous malignancy affecting men and has the highest mortality rate after lung cancer. Even with early intervention and conventional treatment, 30% to 40% of men experience a recurrence of prostate cancer. That means they will need further treatment. Some experts think cryotherapy is an option for treating recurrent prostate cancer. Optical coherence tomography (OCT) has also been adapted for prostate cancer and has been demonstrated to monitore the dynamic process of laser and radiofrequency ablation and identify benign and malignant microscopic structures in the prostate gland ex vivo.